Previous studies from this laboratory have shown that treatment of rat hepatoma Fao cells with N-methyl-N'-nitro-N-nitrosoguanidine caused a concurrent 50 to 80% inhibition of both dexamethasone (DEX)-inducible tyrosine aminotransferase (TAT) enzyme activity and the steady-state levels of DEX-induced TAT RNA. These findings have been confirmed using the parental H4IIEC hepatoma cell clone. Similar results have now been obtained in whole animals. Administration of dimethylnitrosamine (DMN) to rats caused a dose-dependent decrease in DEX-inducible TAT activity, while the carcinogen had little effect on basal levels of TAT expression. DMN exerted its maximal inhibitory effects when administered 2-3 hr prior to induction with DEX. RNA blot analysis demonstrated that the decrease in DEX-inducible TAT enzyme activity could be accounted for by a similar decrease of total steroid-induced TAT RNA. DMN also decreased the levels of DEX-induced glutamine synthetase RNA. Work has continued on the effect of polyoma virus middle-T (mT) gene expression on the cytoskeleton. The mr-mediated increase in alpha-tubulin RNA levels was shown to correlate with a disruption of the microtubule architecture. This laboratory has also been studying the role of drug metabolism in determining susceptibility to chemical carcinogens. Previous studies have shown that fetuses of inducer nonresponsive mothers have higher incidences of lung and liver tumors, and this was shown to be correlated with a more sustained induction of aryl hydrocarbon hydroxylase activity in these fetuses. These results have been extended to the molecular level and shown to be due to a prolonged induction of CYPIA1 RNA. Experiments with fetal rats have shown that CYPIA1 expression as a result of exposure to environmental toxicants exhibited the same kinetic parameters as seen in fetal mice. Thus, earlier time points (about 4 hr) should be used to assess the results of environmental chemicals on CYPIA1 induction.